Aberrant expression of LGALS3BP drives an unfavorable prognosis and more aggressive in HCC via regulating PI3K/AKT signaling.

Lectin galactoside-binding soluble 3-binding protein (LGALS3BP) is associated with cancer metastasis and is a promising prognostic marker in neoplasms. In hepatocellular carcinoma (HCC), the prognostic impact and pro-metastatic function of LGALS3BP remain unclear. This study evaluated the endogenous LGALS3BP expression in HCC tissue and its association with prognosis. LGALS3BP protein levels were significantly elevated in clinical HCC tissues and cell lines. Increased LGALS3BP expression was closely associated with disease progression in HCC patients, and they also exhibited an unfavorable prognosis. Furthermore, the knockdown of LGALS3BP inhibited the growth, migration, and invasion of HCC cells in vitro. In mice xenografts, silencing LGALS3BP significantly inhibited tumor cell growth in vivo. Mechanically, upon LGALS3BP depletion, the tumor-suppressive function was dependent on inactivating Phosphatidylinositol 3-kinase (PI3K)/V-akt murine thymoma viral oncogene homolog (AKT) signaling pathway. Collectively, these findings suggest that LGALS3BP employs a pro-tumorigenic function in HCC and may be a promising HCC prognostic marker.

Effects of storage and processing on the residual distribution and behavior of five preservatives and their metabolites in pomegranate.

Pomegranate are often treated with preservatives during storage. This study investigated the effects of storage and food processing on the residual behavior of the five commonly used preservatives (prochloraz, thiophanate-methyl, pyrimethanil, imazalil, and difenoconazole) and their metabolites in pomegranate and its products. The LOQs for all target compounds were 0.001 mg kg-1. The residue levels of five preservatives in the calyx was highest, followed by the peel, stalk, septum, umbilicus, and seed. For the migration ability, the five preservatives from pomegranate peel to seed was negatively correlated with their octanol/water partition coefficients. The processing factors of each procedures of juice, wine, vinegar, and pectin processing were <1. Nevertheless, the PF values in drying peel during the overall process ranged from 1.26 to 4.09. Hence, it is worth noting that consumption of pomegranate essential oil and drying peel may pose a potential risk to the health of consumers.

Combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and network pharmacology to reveal the key effective compounds and mechanism of Shengxian decoction for ameliorating doxorubicin cardiotoxicity.

Shengxian decoction, a traditional Chinese medicinal prescription, has been shown to alleviate doxorubicin-induced chronic heart failure. This study established an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method to separate and characterize the complex chemical compositions of Shengxian decoction, and the absorbed compounds in the bio-samples of the cardiotoxicity rats with chronic heart failure after its oral delivery. Note that 116 chemical compounds were identified from Shengxian decoction in vitro, 81 more than previously detected. Based on the three-dimensional data of these compounds, 28 absorbed compounds were confirmed in vivo. Network pharmacology and molecular docking experiments indicated that timosaponin B-II, timosaponin A-III, gitogenin, and 7,8-didehydrocimigenol were recognized as the key effective compounds to exert effects against doxorubicin cardiotoxicity by acting on targets such as caspase 3, cyclin-dependent kinase 1, cyclin-dependent kinase 4, receptor tyrosine-protein kinase erbB-2, and mitogen-activated protein kinase 1 in p53 and phosphatidylinositol 3-kinase-Akt signaling pathways. This study developed the understanding of the composition of Shengxian decoction for the treatment of doxorubicin cardiotoxicity, as well as a feasible strategy to elucidate the effective constituents in traditional Chinese medicines.

Dissipation behavior and risk assessment of imidacloprid and its metabolites in apple from field to products.

Pesticides play vital roles in controlling pests and boosting crop yields. Imidacloprid is widely used all over the world and may form in agricultural products. The presence of pesticide residues in apples raises serious health concerns. Understanding the residual fate of imidacloprid is critical for food safety and human health. In this study, the dissipation behavior, metabolism, household processing and risk assessment of imidacloprid and its metabolites in apple were investigated from filed to products. Field experiment results suggested that the half-lives of imidacloprid at 5 times the recommended dosage was 1.5 times that of the standard dosage. And the final residues of imidacloprid were less than the established maximum residue limits (MRLs). Clarification and simmering had little effect on the reduction the residues of imidacloprid and its metabolites. The calculated processing factors were lower than 1 for imidacloprid and its metabolites, implying that the residual ratios of imidacloprid and its metabolites in each steps of the food processing were reduced. The risk quotients were <1 for all Chinese people, indicating that acceptable risks associated with dietary exposure to imidacloprid in apple. However, the higher risks were observed in young people than adults, and females faced higher risks than males. Given high residue levels in pomace, imidacloprid and its metabolites should be further studied in commercial byproducts.

Microglial CMPK2 promotes neuroinflammation and brain injury after ischemic stroke.

Neuroinflammation plays a significant role in ischemic injury, which can be promoted by oxidized mitochondrial DNA (Ox-mtDNA). Cytidine/uridine monophosphate kinase 2 (CMPK2) regulates mtDNA replication, but its role in neuroinflammation and ischemic injury remains unknown. Here, we report that CMPK2 expression is upregulated in monocytes/macrophages and microglia post-stroke in humans and mice, respectively. Microglia/macrophage CMPK2 knockdown using the Cre recombination-dependent adeno-associated virus suppresses the inflammatory responses in the brain, reduces infarcts, and improves neurological outcomes in ischemic CX3CR1Cre/ERT2 mice. Mechanistically, CMPK2 knockdown limits newly synthesized mtDNA and Ox-mtDNA formation and subsequently blocks NLRP3 inflammasome activation in microglia/macrophages. Nordihydroguaiaretic acid (NDGA), as a CMPK2 inhibitor, is discovered to reduce neuroinflammation and ischemic injury in mice and prevent the inflammatory responses in primary human monocytes from ischemic patients. Thus, these findings identify CMPK2 as a promising therapeutic target for ischemic stroke and other brain disorders associated with neuroinflammation.

xWAS analysis in neuropsychiatric disorders by integrating multi-molecular phenotype quantitative trait loci and GWAS summary data.

BACKGROUND: Integrating quantitative trait loci (QTL) data related to molecular phenotypes with genome-wide association study (GWAS) data is an important post-GWAS strategic approach employed to identify disease-associated molecular features. Various types of molecular phenotypes have been investigated in neuropsychiatric disorders. However, these findings pertaining to distinct molecular features are often independent of each other, posing challenges for having an overview of the mapped genes. METHODS: In this study, we comprehensively summarized published analyses focusing on four types of risk-related molecular features (gene expression, splicing transcriptome, protein abundance, and DNA methylation) across five common neuropsychiatric disorders. Subsequently, we conducted supplementary analyses with the latest GWAS dataset and corresponding deficient molecular phenotypes using Functional Summary-based Imputation (FUSION) and summary data-based Mendelian randomization (SMR). Based on the curated and supplemented results, novel reliable genes and their functions were explored. RESULTS: Our findings revealed that eQTL exhibited superior ability in prioritizing risk genes compared to the other QTL, followed by sQTL. Approximately half of the genes associated with splicing transcriptome, protein abundance, and DNA methylation were successfully replicated by eQTL-associated genes across all five disorders. Furthermore, we identified 436 novel reliable genes, which enriched in pathways related with neurotransmitter transportation such as synaptic, dendrite, vesicles, axon along with correlations with other neuropsychiatric disorders. Finally, we identified ten multiple molecular involved regulation patterns (MMRP), which may provide valuable insights into understanding the contribution of molecular regulation network targeting these disease-associated genes. CONCLUSIONS: The analyses prioritized novel and reliable gene sets related with five molecular features based on published and supplementary results for five common neuropsychiatric disorders, which were missed in the original GWAS analysis. Besides, the involved MMRP behind these genes could be given priority for further investigation to elucidate the pathogenic molecular mechanisms underlying neuropsychiatric disorders in future studies.

Crystal-Site Engineering of Novel Na3KMg7(PO4)6-x(BO3)x:Eu2+ Phosphors for Full-Spectrum Lighting.

The "cyan gap" is the bottleneck problem in violet-driven full-spectrum white-light-emitting diodes (wLEDs) in healthy lighting. Accordingly, we develop a novel broadband-blue-cyan emission Na3KMg7(PO4)6-x(BO3)x:Eu2+ (NKMPB:Eu2+) phosphor via crystal-site engineering. This phosphor is derived from the Na3KMg7(PO4)6:Eu2+ phosphor, which shows desired abundant cyan emissive components. A comparative study is conducted to reveal the microstructure-property relationship and the key influential factors to its spectrum distribution. It can be found that the introduced (BO3)3- units can manipulate the site-selective occupation of Eu2+ activators, asymmetrically broadening the emission spectrum in NKMPB:Eu2+. Considering detailed luminescence performance analysis and the density functional theory calculations, a new substitution pathway of Eu2+ is created by substituting (PO4)3- with (BO3)3- units, making partial Eu2+ ions enter the Mg2+ (CN = 5, CN = 6) crystallographic sites, and yielding an extra emission band at 600 nm (16667 cm-1) and especially 501 nm (19960 cm-1). Meanwhile, a high-color-quality full-spectrum-emitting wLEDs was fabricated, upon 100 mA forward-bias current driven. Due to the achieved extra cyan emissive components of NKMPB:Eu2+, the constructed NKMPB:Eu2+-based wLEDs show better color rendering ability (∼90.9) than that of Na3KMg7(PO4)6:Eu2+-based wLEDs (∼86.3), and also demonstrate its great potential in full-spectrum healthy lighting.

Application of Hyperspectral Technology with Machine Learning for Brix Detection of Pastry Pears.

Sugar content is an essential indicator for evaluating crisp pear quality and categorization, being used for fruit quality identification and market sales prediction. In this study, we paired a support vector machine (SVM) algorithm with genetic algorithm optimization to reliably estimate the sugar content in crisp pears. We evaluated the spectral data and actual sugar content in crisp pears, then applied three preprocessing methods to the spectral data: standard normal variable transformation (SNV), multivariate scattering correction (MSC), and convolution smoothing (SG). Support vector regression (SVR) models were built using processing approaches. According to the findings, the SVM model preprocessed with convolution smoothing (SG) was the most accurate, with a correlation coefficient 0.0742 higher than that of the raw spectral data. Based on this finding, we used competitive adaptive reweighting (CARS) and the continuous projection algorithm (SPA) to select key representative wavelengths from the spectral data. Finally, we used the retrieved characteristic wavelength data to create a support vector machine model (GASVR) that was genetically tuned. The correlation coefficient of the SG-GASVR model in the prediction set was higher by 0.0321 and the root mean square prediction error (RMSEP) was lower by 0.0267 compared with those of the SG-SVR model. The SG-CARS-GASVR model had the highest correlation coefficient, at 0.8992. In conclusion, the developed SG-CARS-GASVR model provides a reliable method for detecting the sugar content in crisp pear using hyperspectral technology, thereby increasing the accuracy and efficiency of the quality assessment of crisp pear.

Upconversion luminescence through dynamically regulating the depletion of Ho3+: 5I6 level for speed sensing.

In this work, a strategy for dynamically adjusting the upconversion luminescence (UCL) color of NaGdF4:Yb3+/Ho3+/Ce3+/Sc3+ is reported based on a phosphor wheel. It has been demonstrated that the rotation-dependent UCL mainly originated from the regulation of depletion mode for the Ho3+: 5I6 level. Due to the dominant linear decay, a high-pure red UCL is observed under the steady-state excitation. However, as the proportion of the steady-state excitation decreases, the green-red emission intensity ratio gradually increases, followed by the color conversion from red to green. An approximate physical model is proposed to understand the dependence of IG/IR on rotation speed. We not only report a UCL material that shows potential application in velocity sensing but also provide new insights into wheel-based dynamic UCL regulation.

T Cell Subsets and Immune Homeostasis.

T cells are a heterogeneous group of cells that can be classified into different subtypes according to different classification methods. The body's immune system has a highly complex and effective regulatory network that allows for the relative stability of immune system function. Maintaining proper T cell homeostasis is essential for promoting protective immunity and limiting autoimmunity and tumor formation. Among the T cell family members, more and more T cell subsets have gradually been characterized. In this chapter, we summarize the functions of some key T cell subsets and their impact on immune homeostasis.

The impact of the length of proximal margin on the prognosis in adenocarcinoma of gastroesophageal junction: A real-world study and strategies.

BACKGROUND: The optimal proximal margin (PM) length for Siewert II/III adenocarcinoma of the esophagogastric junction (AEJ) remains unclear. This study aimed to determine the optimal PM length using an abdominal approach to guide surgical decision-making. METHODS: A prospective study analyzed 304 consecutive patients diagnosed with Siewert II/III AEJ between January 2019 and December 2021. Total gastrectomy was performed via the abdominal approach, and PM length was measured on fixed gross specimens. X-Tile software determined the optimal PM cut-point based on progression-free survival (PFS). Univariate analyses compared baseline characteristics across PM groups, while survival analyses utilized Kaplan-Meier estimation and Cox proportional hazards regression for assessing the impact of margin length on survival. Multivariable analyses were conducted to adjust for confounding variables. RESULTS: The study included 264 AEJ cases classified as Siewert II (71.97%) or III (28.03%). The median gross PM length was 1.0 cm (IQR: 0.5 cm-1.5 cm, range: 0 cm-6 cm). PM length ≥1.2 cm was associated with a lower risk of disease progression compared to PM length 0.4 cm on PFS (HR = 0.41, 95% CI 0.20-0.84, P = 0.015). Moreover, PM ≥ 1.2 cm improved prognosis in subgroups of T4 or N3, tumor size <4 cm, Siewert II, and Lauren classification. CONCLUSIONS: For Siewert type II/III AEJ, a proximal margin length ≥1.2 cm (1.65 cm in situ) is associated with improved outcomes. These findings offer valuable insights into the association between PM length and outcomes in Siewert II/III AEJ, providing guidance for surgical approaches and aiding clinical decision-making to enhance patient outcomes.

[Advances in the study of the actin nucleation factor Spire].

There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers and binding actin to the growing end of the microfilament. As early as 1999, Wellington et al. identified Spire as an actin nucleating agent, however, over the years, most studies have focused on Arp2/3 and Formin proteins; there has been relatively less research on Spire as a member of the actin nucleating factors. Recent studies have shown that Spire is involved in the vesicular transport through the synthesis of actin and plays an important role in neural development. In this paper, we reviewed the structure, expression and function of Spire, and its association with disease in order to identify meaningful potential directions for studies on Spire.

Integration of multi-omics summary data reveals the role of N6-methyladenosine in neuropsychiatric disorders.

N6-methyladenosine (m6A) methylation regulates gene expression/protein by influencing numerous aspects of mRNA metabolism and contributes to neuropsychiatric diseases. Here, we integrated multi-omics data and genome-wide association study summary data of schizophrenia (SCZ), bipolar disorder (BP), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer's disease (AD), and Parkinson's disease (PD) to reveal the role of m6A in neuropsychiatric disorders by using transcriptome-wide association study (TWAS) tool and Summary-data-based Mendelian randomization (SMR). Our investigation identified 86 m6A sites associated with seven neuropsychiatric diseases and then revealed 7881 associations between m6A sites and gene expressions. Based on these results, we discovered 916 significant m6A-gene associations involving 82 disease-related m6A sites and 606 genes. Further integrating the 58 disease-related genes from TWAS and SMR analysis, we obtained 61, 8, 7, 3, and 2 associations linking m6A-disease, m6A-gene, and gene-disease for SCZ, BP, AD, MDD, and PD separately. Functional analysis showed the m6A mapped genes were enriched in "response to stimulus" pathway. In addition, we also analyzed the effect of gene expression on m6A and the post-transcription effect of m6A on protein. Our study provided new insights into the genetic component of m6A in neuropsychiatric disorders and unveiled potential pathogenic mechanisms where m6A exerts influences on disease through gene expression/protein regulation.

Novel genetic loci of inhibitory control in ADHD and healthy children and genetic correlations with ADHD.

Cumulative evidence has showed the deficits of inhibitory control in patients with attention deficit hyperactivity disorder (ADHD), which is considered as an endophenotype of ADHD. Genetic study of inhibitory control could advance gene discovery and further facilitate the understanding of ADHD genetic basis, but the studies were limited in both the general population and ADHD patients. To reveal genetic risk variants of inhibitory control and its potential genetic relationship with ADHD, we conducted genome-wide association studies (GWAS) on inhibitory control using three datasets, which included 783 and 957 ADHD patients and 1350 healthy children. Subsequently, we employed polygenic risk scores (PRS) to explore the association of inhibitory control with ADHD and related psychiatric disorders. Firstly, we identified three significant loci for inhibitory control in the healthy dataset, two loci in the case dataset, and one locus in the meta-analysis of three datasets. Besides, we found more risk genes and variants by applying transcriptome-wide association study (TWAS) and conditional FDR method. Then, we constructed a network by connecting the genes identified in our study, leading to the identification of several vital genes. Lastly, we identified a potential relationship between inhibitory control and ADHD and autism by PRS analysis and found the direct and mediated contribution of the identified genetic loci on ADHD symptoms by mediation analysis. In conclusion, we revealed some genetic risk variants associated with inhibitory control and elucidated the benefit of inhibitory control as an endophenotype, providing valuable insights into the mechanisms underlying ADHD.

The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.

Purpose: The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. Patients and Methods: An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. Results: Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. Conclusion: It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.

Attention Mechanism and LSTM Network for Fingerprint-Based Indoor Location System.

The demand for precise indoor localization services is steadily increasing. Among various methods, fingerprint-based indoor localization has become a popular choice due to its exceptional accuracy, cost-effectiveness, and ease of implementation. However, its performance degrades significantly as a result of multipath signal attenuation and environmental changes. In this paper, we propose an indoor localization method based on fingerprints using self-attention and long short-term memory (LSTM). By integrating a self-attention mechanism and LSTM network, the proposed method exhibits outstanding positioning accuracy and robustness in diverse experimental environments. The performance of the proposed method is evaluated under two different experimental scenarios, which involve 2D and 3D moving trajectories, respectively. The experimental results demonstrate that our approach achieves an average localization error of 1.76 m and 2.83 m in the respective scenarios, outperforming the existing state-of-the-art methods by 42.67% and 31.64%.

Interfacial π-p Electron Coupling Prompts Hydrogen Evolution Reaction Activity in Acidic Electrolyte.

The thermodynamically stable 2H-phase MoS2 is a brilliant material toward hydrogen evolution reaction (HER) owing to its excellent Gibbs free energy of hydrogen adsorption. Nevertheless, the poor intrinsic properties of 2H-MoS2 limit its electrocatalytic performances toward HER. In this work, graphitic carbon nitride covalently bridging 2H-MoS2 (MoS2/GCN) is proposed to construct robust HER electrocatalysts. The strong π-p electron coupling between the delocalized π electrons of GCN and the localized p electrons of S atoms sufficiently expose active sites and accelerate the reaction kinetics. To be specific, MoS2/GCN exhibits remarkable HER activity (160 mV at 10 mA·cm-2) and long-term durability. Importantly, MoS2/GCN also provides great potential for industrial application. Density functional theory (DFT) calculations disclose that the π-p electron coupling at the MoS2/GCN interface regulates the electronic structure of S atoms, consequently providing enhanced HER performance. This work presents a feasible pathway to develop advanced electrocatalysts for energy conversions.

Re-injection off-axis integrated cavity output spectroscopy for the simultaneous detection of N2O, H2O and CO with a mid-infrared QCL laser.

Off-axis integrated cavity output spectroscopy (OA-ICOS) has attracted much interest because it potentially allows highly sensitive field measurements with robust optical alignment. In this paper, a novel instrument that employs a high-finesse optical cavity as an absorption cell has been developed for sensitive measurements of multi-component gases N2O, H2O and CO in the atmosphere based on a mid-infrared quantum cascade laser (QCL) and OA-ICOS. In order to improve the energy utilization and increase the signal-to-noise ratio (SNR) of the signal, a new type of optical path structure of the laser re-injection method is adopted. Furthermore, the system performance can be effectively improved by using a new intervention method of injecting radio frequency (RF) white noise into a laser driver to suppress cavity mode noise and combining the wavelength modulation method (WMS). We compared the sensitivity of the second harmonic signal demodulation between the re-injection method and the standard OA-ICOS, and the SNR increased by 2.68 times compared to the latter. Analysis of the spectral measurements with Allan variance indicates that within an integration time of 1 s, the measurement accuracy of N2O, H2O, and CO is 6.71 ppb, 13.945 ppm, and 1.81 ppb, respectively, and within an integration time of 820 s, the measurement accuracy of N2O, H2O, and CO can be further improved to 1.26 ppb, 2.089 ppm, and 172 ppt, respectively. Our approach represents an underlying analytical method that provides guidelines for monitoring of representative gases in the atmosphere, industrial processes, emergency safety, etc.

Highly Bright and Stable Lead-Free Double Perovskite White Light-Emitting Diodes.

Lead-free double perovskites (DPs) are emerging highly stable emitters with efficient broadband self-trapped exciton (STE) photoluminescence (PL), but their low electroluminescent (EL) efficiency is a critical shortcoming. This work promotes the external quantum efficiency (EQE) and luminance of DP-based white light-emitting diode (wLED) with a normal device structure to 0.76% and 2793 cd m-2 via two modifications: This work prevents the formation of adverse metallic silver, spatially confined STE, and lowers local site symmetry in Cs2 Na0.4 Ag0.6 In0.97 Bi0.03 Cl6 DP by terbium doping; and this work develops a guest-host strategy to improve film morphology, reduce defect density, and increase carrier mobility. These alterations cause substantial increase in STE radiative recombination and charge injection efficiency of perovskite layer. Finally, pure white EL with ideal color coordinates of (0.328, 0.329) and a record-breaking optoelectronic performance is achieved by introducing additional green carbon dots in LED to fill the deficient green component.